TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2680	8263;8264;8265	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014
N2AB	2680	8263;8264;8265	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014
N2A	2680	8263;8264;8265	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014
N2B	2634	8125;8126;8127	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014
Novex-1	2634	8125;8126;8127	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014
Novex-2	2634	8125;8126;8127	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014
Novex-3	2680	8263;8264;8265	chr2:178771289;178771288;178771287	chr2:179636016;179636015;179636014

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-16
• Domain position: 60
• Structural Position: 143
• Q(SASA): 0.3139
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/T	None	None	0.002	N	0.093	0.064	0.0954503805726	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.4866	ambiguous	0.5039	ambiguous	-0.983	Destabilizing	0.836	D	0.37	neutral	None	None	None	None	N
A/D	0.1803	likely_benign	0.1848	benign	-1.522	Destabilizing	0.351	N	0.41	neutral	N	0.323328426	None	None	N
A/E	0.1603	likely_benign	0.1606	benign	-1.64	Destabilizing	0.418	N	0.365	neutral	None	None	None	None	N
A/F	0.2263	likely_benign	0.2427	benign	-1.333	Destabilizing	0.716	D	0.42	neutral	None	None	None	None	N
A/G	0.1389	likely_benign	0.1385	benign	-0.92	Destabilizing	0.183	N	0.301	neutral	N	0.347960948	None	None	N
A/H	0.3599	ambiguous	0.3742	ambiguous	-0.873	Destabilizing	0.983	D	0.39	neutral	None	None	None	None	N
A/I	0.1381	likely_benign	0.1609	benign	-0.63	Destabilizing	None	N	0.123	neutral	None	None	None	None	N
A/K	0.2945	likely_benign	0.295	benign	-0.999	Destabilizing	0.418	N	0.363	neutral	None	None	None	None	N
A/L	0.1393	likely_benign	0.1493	benign	-0.63	Destabilizing	0.061	N	0.285	neutral	None	None	None	None	N
A/M	0.1591	likely_benign	0.1762	benign	-0.378	Destabilizing	0.716	D	0.358	neutral	None	None	None	None	N
A/N	0.1426	likely_benign	0.1507	benign	-0.771	Destabilizing	0.418	N	0.433	neutral	None	None	None	None	N
A/P	0.3278	likely_benign	0.2946	benign	-0.65	Destabilizing	0.794	D	0.402	neutral	N	0.344279689	None	None	N
A/Q	0.2466	likely_benign	0.2483	benign	-1.132	Destabilizing	0.836	D	0.361	neutral	None	None	None	None	N
A/R	0.2915	likely_benign	0.2834	benign	-0.441	Destabilizing	0.716	D	0.376	neutral	None	None	None	None	N
A/S	0.0824	likely_benign	0.0829	benign	-0.981	Destabilizing	0.021	N	0.131	neutral	N	0.34620646	None	None	N
A/T	0.0728	likely_benign	0.0777	benign	-1.033	Destabilizing	0.002	N	0.093	neutral	N	0.348339449	None	None	N
A/V	0.0846	likely_benign	0.0926	benign	-0.65	Destabilizing	0.001	N	0.093	neutral	N	0.316512458	None	None	N
A/W	0.6878	likely_pathogenic	0.7042	pathogenic	-1.487	Destabilizing	0.983	D	0.44	neutral	None	None	None	None	N
A/Y	0.3657	ambiguous	0.3855	ambiguous	-1.131	Destabilizing	0.836	D	0.415	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.